Influence of septum stimulation and lesion on changes of heart rate elicited by hypothalamic self-stimulation [proceedings].
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Self-stimulation of the subfornical organ and lateral hypothalamus: differential effects of atropine and methysergide.
The effects of cholinergic blockade of neurons by atropine or serotonergic blockade by methysergide was investigated in rats responding for brain-stimulation reward. Bipolar stimulating electrodes were placed either in the subfornical organ (SFO) or the lateral hypothalamus (LH). Atropine sulphate and methysergide significantly suppressed self-stimulation of the SFO but not of the LH, suggesting that cholinergic and serotonergic neurons are involved in brain-stimulation reward associated with this site.
Amphetamine↗
Self-stimulation responses are altered following long-term but not short-term treatment with clorgyline.
Clorgyline (a selective monoamine oxidase-inhibiting antidepressant) given chronically facilitated hypothalamic self-stimulation in rats, while acute treatment was without effect. Furthermore, long-term but not short-term clorgyline treatment significantly attenuated the suppressive effect of the selective alpha 2-adrenergic agonist clonidine on this behavior. These findings suggest that adaptative alterations in the modulation of rewarded behavior by inhibitory presynaptic noradrenergic receptors may be involved in antidepressant efficacy.
Animals↗
Changes in posterior hypothalamic self-stimulation following experimental cerebral infarction in the rat.
Bioplar stimulating electrodes were placed bilaterally in the posterior hypothalamus of rats following which the animals were shaped for intracranial self-stimulation (ICSS). When ICSS rates were stable for 1 wk, the right middle cerebral artery was ligated. During the 25-day postinfarction period, the rate of ICSS at specified current values was compared with preoperative rates. At 2 days after operation, there was a 33% decrease in the maximum frequency of ipsilateral ICSS. However, by 8 days after experimental stroke, there was a 16% increase in the maximal rate of ICSS above the preoperative value, and the rate returned to control levels by 20 days after surgery. The minimum current necessary to elicit the maximal rate of response also changed in a biphasic manner, i.e., the minimum required current was greater than preoperative control levels until 8 days after operation but then dropped below control level until 20 days postoperatively. There were no changes in the current or rate of response in the contralateral electrode. These results are discussed in relation to what may be the underlying neurophysiological changes causing these biphasic alterations in ICSS.
Animals↗
Characterization of self-stimulation elicited from rat dorsolateral pariaqueductal gray.
Rats were stereotaxically implanted with chronic bipolar electrodes aimed at the periaqueductal central gray (PCG) and were subsequently tested for intracranial self-stimulation (ICSS) behavior. Consistent and reliable ICSS behavior was elicited from both the midventral and dorsolateral portions of the PCG, the latter result occurring in loci previously reported as predominantly aversive. Midventral PCG ICSS rates were significantly higher than dorsolateral PCG ICSS rates. The higher rates were not accounted for by either current intensity used or motor artifacts. Moreover, both sites displayed reliable ICSS behavior characterized by regular low-variability rates and no seizure activity, seen with other brainstem ICSS sites, but unlike diencephalic and telencephalic ICSS behavior which is characterized by irregular bursts of responding which are highly variable and sometimes accompanied by seizures. The differential ICSS responsivity between PCG structures suggests that they may be mediated by different anatomically-localizable substrates.
Animals↗
Atypical antipsychotics produce within-session decrements on self-stimulation of the rat medial prefrontal cortex.
It has been described that "typical" antipsychotic drugs (APDs) induce characteristic within-session response decrements in operant behaviors, including intracranial self-stimulation (ICSS). In contrast, recent reports have shown that in food operant behavior, clozapine and a number of "atypical" APDs do not give rise to within-session effects. However, to elucidate whether or not this is a common property of atypical APDs, their effects on other operant models need to be studied. To address this question we investigated the temporal pattern of ICSS responding, after systemic administration of five atypical APDs and the typical antipsychotic, haloperidol. Rats were trained to lever press for electrical stimulation at the medial prefrontal cortex (mPFC), and response rates were recorded during each 3-min period of the 15-min session. Significant within-session response decrements on mPFC ICSS were observed with haloperidol, risperidone, sertindole and olanzapine but not with clozapine or ziprasidone. The magnitude of within-session decline produced by the APDs tested was positively correlated with their affinity for dopamine D2 receptors. The results show for the first time that atypical APDs are capable to induce within-session decrements on ICSS behavior, and suggest that this particular temporal pattern of responding is not exclusively characteristic of typical APDs. The results are also consistent with the hypothesis that the ability of APDs to induce greater within-session effects may be related, in part, to potent D2 antagonism.
Animals↗
[Roles of noradrenergic and dopaminergic systems in the self-stimulation behavior of the substantia nigra].
A bipolar electrode was stereotaxically implanted in the substantia nigra of male albino Wistar-Imamichi rats. 1) Rats lifted and turned their heads and contralateral forelimb towards the contralateral side to the electrode during the substantia nigral self-stimulation (SS) behavior. 2) Methamphetamine facilitated the SS dose-dependently in the "threshold"-intensity reinforcement. The pretreatment of imipramine facilitated the effects of methamphetamine. 3) FLA63 and U-14,624, dopamine beta-hydroxylase inhibitors, suppressed the SS in the moderate-intensity reinforcement. 4) Apomorphine, stimulant of dopamine receptor, did not facilitate, but rather inhibited the SS dose-dependently in the "threshold"-intensity reinforcement. 5) l-Norepinephrine injected into the lateral ventricle facilitated the SS dose-dependently. On the other hand, dopamine had no marked effects. 6) These results suggest that the noradrenergic system in the brain plays a more important role in the positive reinforcement of the substantia nigral SS behavior than does the dopaminergicsystem.
Animals↗
Pharmaco-ontogeny of reward: enhancement of self-stimulation by D-amphetamine and cocaine in 3- and 10-day-old rats.
Electrodes were implanted in various forebrain sites in 3- and 10-day-old rat pups that were allowed to nudge a pole for electrical stimulation of those areas. After 5 h pups were injected with amphetamine, cocaine or saline and the change in responding noted. Both stimulants, at relatively high doses, enhanced responding on the pole that produced stimulation to a greater extent than responding on a non-active pole. At lower doses, responding on both the active and inactive poles were enhanced equally. These effects lasted 2-3 h. Histological analyses showed that the most sensitive loci that were consistently enhanced by these stimulants included the medial forebrain bundle, nucleus accumbens, anterior olfactory nucleus and olfactory tubercle. The results suggest that the biological mechanisms by which these drugs enhance self-stimulation in adult animals are present in neonates.
Aging↗
Naloxone and diprenorphine reduce responding for brain self-stimulation in a fixed-ratio schedule in rats.
Rats were implanted with bipolar stimulating electrodes in the midbrain-central gray area (MID-CG) and trained to lever-press for intracranial self-stimulation (ICSS) on a continuous reinforcement schedule (CRF). When behavior was stable, animals were tested in 30 min ICSS sessions following the administration of either naloxone or diprenorphine, both over the dose-range 0.001-10 mg/kg, or with vehicle. Following testing on the CRF schedule, animals were re-trained on a fixed-ratio:30 (FR:30) schedule. When behavior had again stabilized, testing with naloxone, diprenorphine and vehicle was repeated. In the CRF tests, neither naloxone nor diprenorphine had any effects on response rates over the 10,000-fold dose-range used. In the FR:30 tests, however, both drugs significantly reduced response rates at the 10 mg/kg dose, and the reduction produced by naloxone was significantly greater than that produce by diprenorphine. These results suggested that diprenorphine is qualitatively similar to naloxone in altering the rate of responding maintained by ICSS, but is less potent than the prototypical opioid antagonist in this paradigm.
Animals↗
Intracranial self-stimulation motivates treadmill running in rats.
Most animal running models have traditionally used aversive motivators to induce exercise tasks. This study demonstrates treadmill running motivated by reinforcement of intracranial self-stimulation (ICSS), providing an alternative model with which to study physiological responses to exercise. Twenty-nine male Sprague-Dawley rats were stereotaxically implanted with bipolar electrodes aimed at the ventral tegmental area of the brain. After 7 days of operant lever-press training for ICSS, rats that pressed at least 50 presses/min were randomly divided into three conditions: exercise-reinforcing brain stimulation (Ex-St), exercise-aversive shock (Ex-Sh), and sedentary controls (C). Ex-St and Ex-Sh ran for 30 min at 25 m/min at 5% grade for 2 wk with ICSS and electric shock as the motivator, respectively, while C did not run. At the end of 2 wk, Ex-St and Ex-Sh performed an endurance run. Results show that Ex-St ran longer than Ex-Sh [63 +/- 10 vs. 42 +/- 10 (SD) min; P less than 0.05]. HR was higher in Ex-St than in C (P less than 0.05). Rectal temperature increased similarly in both exercise groups. This model provides a highly effective method to motivate treadmill running in rats and as such can be used to characterize physiological responses to exercise without the potentially confounding influence of stress associated with an aversive shock motivator.
Animals↗
Hippocampus modulates self-stimulation reward from the ventral tegmental area in the rat.
Rats with electrodes in the ventral tegmental area were tested for the threshold of intracranial reward using a rate insensitive self-stimulation procedure. It was found that an electrolytic lesion of a part of the dorsal hippocampus induced a marked decrease in the variation of thresholds across rats, while the mean reward level did not change. This indicates that a factor is removed, by the hippocampal lesion, which causes differences in reward between individual rats. It is suggested that the mesolimbic dopaminergic system is involved in this modulatory influence of the hippocampus on reward.
Animals↗
The effects of dopamine D3/D2 receptor agonists on intracranial self stimulation in the rat.
The effects of the dopamine D3/D2 receptor agonists quinpirole, quinelorane and (+/-)7-OH-DPAT [(+/-) 7-hydroxy-2(N,N-di-n-propylamino) tetralin] on intracranial self-stimulation (ICSS) were investigated. Rats implanted with bipolar electrodes into the lateral hypothalamus were trained to lever press on a continuous reinforcement schedule for positively reinforcing trains of electrical stimulation. Three measures of responding were calculated; the frequency at which responding was 50% of the maximum (M50), the asymptotic response rate and the total area under the curve (AUC) for each frequency sweep. Quinpirole (2.2-66.0 microg/kg SC) significantly increased M50 and reduced both asymptote and AUC. Quinelorane (0.25-79.0 microg/kg SC) had no significant effect on M50 values but significantly reduced both asymptote and AUC. (+/-)7-OH-DPAT (2.5-74.0 microg/kg) did not significantly affect any of the measures. The data show that low doses of quinpirole and quinelorane, but not (+/-)7-OH-DPAT, inhibit ICSS maintained by electrodes in the lateral hypothalamus. Either dopamine D2 or dopamine D3 receptor stimulation may play a role in mediating ICSS inhibition, but studies with more selective receptor agonists and antagonists are required to define the role of each receptor.
Animals↗
[Relation between the frequency of self stimulation and stimulus duration and its correlation with the duration preferred by the animal].
The effect of duration of stimulus addressed to the lateral hypothalamus on self-stimulation (SS) frequency was studied in rabbits. In the first experimental series, durations preferred by the animals were determined. Histograms of pression durations were obtained, and modal (Tm) and mean (T mean) durations were assessed. In the second series, stimuli were used of fixed duration equal to Tm, T mean and multiples to them--longer and shorter impulse bursts. Three types of distribution histograms of pression durations were obtained, which differed from each other by the form of the envelop as well as by variation coefficients of deviation of self regulated durations from the mean (T mean). These parameters were of a character of individual differences independently from localization of the stimulating electrodes tips. SS frequency was maximal when stimulation durations were 2 Tm and 1/2-1/4 T mean. Prolongation or shortening of the stimulation led to weakening of its reinforcing effect. The concept is discussed of two-component mechanism of reaction to stimulation of the SS hypothalamic zones: motivational excitation against the background of current action and positive reinforcement in post-stimulation period.
Animals↗
Different effects of cholecystokinin and satiety on lateral hypothalamic self-stimulation.
The effects of cholecystokinin (CCK) and satiety were compared in animals lever-pressing for rewarding electrical stimulation of the lateral hypothalamus. For some rats, conditions of food deprivation and satiation, respectively, increased or decreased responding whereas the self-stimulation behavior of other rats was unresponsive to these feeding manipulations. CCK, at doses thought to signal satiety, reduced the responding of all rats independent of whether they were, or were not, responsive to real satiety. This same result was obtained with the aversive agent lithium chloride. These data suggest that the reduced feeding observed following CCK administration is due to aversive consequences and not satiety.
Analysis of Variance↗
The basolateral limbic circuit and self-stimulation of the medial prefrontal cortex in the rat.
The effects of lesions of the basolateral nucleus of the amygdala (ABL) and the mediodorsal nucleus of the thalamus (MD) on self-stimulation (SS) of the medial prefrontal cortex (MPC) were investigated. Spontaneous motor activity (SMA) was measured as a control for possible non-specific effects of the lesions. Bilateral electrolytic lesions of ABL or MD produced a parallel transient decrease of SS and SMA. However, combined lesion of ABL and MD produced clearly different effects on both parameters. SMA decreased during the 1st day post-lesion and recovered to control levels by the 3rd day post-lesion. SS, on the contrary, was significantly decreased during the first five days post-lesion and after that time SS rate recovered to control levels. These results suggest the involvement of the basolateral limbic circuit in the neural substate underlying SS behavior of the MPC.
Animals↗
Effects of dopamine D3 preferring compounds on conditioned place preference and intracranial self-stimulation in the rat.
Compounds showing an in vitro binding preference for the dopamine D3 receptor were tested in two models designed to assess positive reinforcement in the rat: intracranial self-stimulation (ICSS) and conditioned place preference (CPP). R-(+)-7-OH-DPAT, a D3 preferring agonist, inhibited ICSS behaviour over a wide dose range. At higher doses, a facilitation of ICSS was seen. In the CPP model, 7-OH-DPAT was inactive except at the highest dose where a significant change in preference was seen. A dose of R-(+)-7-OH-DPAT, that significantly inhibited ICSS behaviour, was combined with a dose of d-amphetamine, that significantly facilitated ICSS behaviour. Surprisingly, this resulted in a significant synergistic facilitation of the amphetamine response. The putative D3 antagonist, U99194A was inactive in the ICSS model but induced significant place preference. The present results suggest that the dopamine D3 receptor, in contrast to the D2 receptor, has an inhibitory influence on reward mechanisms.
Animals↗
Intracranial self-stimulation site specificity: the myth of current spread.
Locus-specificity of intracranial self-stimulation (ICSS) was determined for 78 electrode placements using monophasic stimulation. ICSS rate comparisons between each pole of a bipolar electrode when each served as cathode were made when the anodal source was either the other pole of the bipolar electrode or a skull screw. In hypothalamic areas, medial forebrain bundle electrode tips elicited significantly higher rates than electrode tips of the same bipolar electrodes located in perifornical or far-lateral diencephalic placements. In turn, perifornical electrode tips elicited higher rates than more dorsally or medially placed tips. In dorsal pontine areas, locus coeruleus electrode tips elicited significantly higher rates than more medially or laterally placed tips. In periaqueductal midbrain and substantia nigra placements, tips located along the midline or in the substantia nigra elicited significantly higher rates than tips located lateral to or ventral to those respective structures. Anodal locus did not change these results. These results suggest that ICSS behavior is delimited by and corresponds to neuroanatomically discrete entities and that cathodal, rather than anodal factors seem to most crucially determine ICSS integrity.
Animals↗
Hypothalamic self-stimulation and operant activity in the mottled mutant mouse.
Some behavioural effects of the mottled mutation were studied in the variegated heterozygote female. In mutants, compared to normals, operant activity was increased, whereas hypothalamic self-stimulation was always decreased. These results are discussed relative to the excepted central catecholaminergic disturbances resulting from the mutant gene.
Animals↗